To give evidence-based recommendations for the treatment of cluster headache attacks, for the prophylaxis of cluster headache, for the treatment of paroxysmal hemicranias, and for the treatment of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome

Note: The following were considered but not recommended for treatment of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome: lamotrigine, gabapentin, topiramate, oxcarbazepine, verapamil, intravenous lidocaine, steroids, intravenous phenytoin, and stimulation of the hypothalamus. Lamotrigine is considered first-line treatment.

Methodology

Methods Used to Collect/Select the Evidence

Hand-searches of Published Literature (Secondary Sources)Searches of Electronic Databases

Description of Methods Used to Collect/Select the Evidence

A literature search was performed using the reference databases Medline, Science Citation Index and the Cochrane Library; the keywords used were 'cluster headache', 'paroxysmal hemicrania', 'SUNCT', 'treatment' and 'trial' (last search in March 2009). All papers published in English, German or French were considered when they described a controlled trial or a case series on the treatment of at least five patients (or fewer in paroxysmal hemicrania or short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing [SUNCT] syndrome). In addition, a review book and the German treatment recommendations for cluster headache were considered.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence

Weighting According to a Rating Scheme (Scheme Given)

Rating Scheme for the Strength of the Evidence

Evidence Classification Scheme for a Therapeutic Intervention

Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:

Randomization concealment

Primary outcome(s) is/are clearly defined

Exclusion/inclusion criteria are clearly defined

Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias

Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences

Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e

Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment

All authors performed an independent literature search. The first draft of the manuscript was written by the chairman of the task force. All other members of the task force read the first draft and discussed changes by email. A second draft was then written by the chairman and was again discussed by email. All recommendations had to be agreed to by all members of the task force unanimously. The background of the research strategy and of reaching consensus and the definitions of the recommendation levels used in this paper have been described in the European Federation of Neurological Societies (EFNS) recommendations (see the "Availability of Companion Documents" field).

Rating Scheme for the Strength of the Recommendations

Rating of Recommendations

Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.

As first choice, acute attacks of cluster headache should be treated with the inhalation of 100% oxygen with at least 7 l/min over 15 min (Class II trials) or with the subcutaneous injection of 6 mg sumatriptan or the intranasal application of zolmitriptan 5 mg (Class I trials). As second choice, sumatriptan 20 mg nasal spray can be used (Class I trial) with minor efficacy or more side effects.

Prophylaxis of cluster headache should be first tried with verapamil in a daily dose of at least 240 mg (maximum dose depends on efficacy or tolerability; electrocardiogram [ECG] controls are obligatory with increasing doses). Although no Class I or II trials are available, steroids are clearly effective in cluster headache. Therefore, the use of at least 100 mg oral up to 500 mg intravenous (i.v.) per day methylprednisone (or equivalent corticosteroid) over 5 days (then tapering down) is recommended.

Level B Recommendations

Intranasal lidocaine (4%) can be tried in acute cluster headache attacks if Level A medication is ineffective or contraindicated. Oral zolmitriptan 10 mg is effective in some patients (Class I trial) but high dose produces many side effects and limits practical use.

Methysergide and lithium are drugs of second choice if verapamil is ineffective or contraindicated. Corticosteroids can be used for short courses where bouts are short or to help establish another medicine. Topiramate is promising, but only open trials exist at this point. Melatonin is useful in some patients. Except for lithium, the maximum dose depends on efficacy and tolerability. Ergotamine tartrate is recommended for short-term prophylaxis (Class III studies). In spite of positive Class II studies, pizotifen and intranasal capsaicin should not be used because of side effects.

Level C Recommendations

Baclofen 15 to 30 mg and valproic acid showed possible efficacy and can be tried as drugs of third choice.

Surgical procedures are not indicated in most patients with cluster headache. Patients with intractable chronic cluster headache should be referred to centres with expertise in both destructive and neuromodulatory procedures to be offered all reasonable alternatives before a definitive procedure is conducted.

Treatment of Paroxysmal Hemicrania

Paroxysmal hemicrania is to be treated with indomethacin up to 200 mg (Level A recommendation). Alternatively, verapamil, topiramate, and different nonsteroidal anti-inflammatory drugs (NSAIDs) can be tried (Level C recommendation).

No recommendation can be given for the treatment of SUNCT syndrome. Treatment with lamotrigine (at least 100 mg) is considered the first-line option.

Definitions:

Evidence Classification Scheme for a Therapeutic Intervention

Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:

Randomization concealment

Primary outcome(s) is/are clearly defined

Exclusion/inclusion criteria are clearly defined

Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias

Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences

Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e

Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment

Side effects of verapamil are bradycardia, oedema, constipation, gastrointestinal discomfort, gingival hyperplasia, and dull headache. Regular electrocardiographic (ECG) controls are required to control for an increase in cardiac conduction time. Sometimes, echocardiography can be necessary due to the negative inotropic effects of verapamil.

Major side effects of lithium are hypothyroidosis, tremor, and renal dysfunction. Lithium should be monitored by the plasma level which should be between 0.3 and 1.2 mmol/l. Regular control of liver, renal and thyroid function and of electrolytes is required.

Since there is small but important incidence of pulmonary and retroperitoneal fibrosis, the continuous use of methysergide is limited to a maximum of 6 months.

Main side effects of topiramate and gabapentin are cognitive disturbances, paraesthesias, and weight loss.

Gastrointestinal discomfort and bleedings are the major side effects of indomethacin. Therefore, a proton pump inhibitor should be given in addition.

High morbidity from corticosteroids suggests caution, short courses, and avoidance in chronic cluster headache.

In cluster headache patients, a risk for the development of medication overuse headache has been shown, in particular if there is a comorbidity or a family history of migraine.

Qualifying Statements

Qualifying Statements

This guideline provides the view of an expert task force appointed by the Scientific Committee of the European Federation of Neurological Societies (EFNS). It represents a peer-reviewed statement of minimum desirable standards for the guidance of practice based on the best available evidence. It is not intended to have legally binding implications in individual cases.

The recommendations are based on the scientific evidence from clinical trials and on the expert consensus by this EFNS task force. The legal aspects of drug prescription and drug availability in the different European countries will not be considered.

Implementation of the Guideline

Description of Implementation Strategy

The European Federation of Neurological Societies has a mailing list and all guideline papers go to national societies, national ministries of health, World Health Organisation, European Union, and a number of other destinations. Corporate support is recruited to buy large numbers of reprints of the guideline papers and permission is given to sponsoring companies to distribute the guideline papers from their commercial channels, provided there is no advertising attached.

This NGC summary was completed by ECRI on April 11, 2007. The information was verified by the guideline developer on May 15, 2007. This summary was updated by ECRI Institute on May 1, 2009 following the U.S. Food and Drug Administration advisory on antiepileptic drugs. This summary was updated by ECRI Institute on January 8, 2010 following the U.S. Food and Drug Administration advisory on Valproate sodium. This summary was updated by ECRI Institute on July 26, 2010 following the U.S. Food and Drug Administration (FDA) advisory on Proton Pump Inhibitors (PPI). This summary was updated by ECRI Institute on September 15, 2010 following the U.S. Food and Drug Administration advisory on Lamictal (lamotrigine). This summary was updated by ECRI Institute on April 13, 2011 following the U.S. Food and Drug Administration advisory on Topamax (topiramate). This summary was updated by ECRI Institute on February 20, 2012. This summary was updated by ECRI Institute on July 10, 2013 following the U.S. Food and Drug Administration advisory on Valproate.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the Blackwell-Synergy copyright restrictions.

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